FASEB J. 2025 Dec 15;39(23):e71309. doi: 10.1096/fj.202503502R.
ABSTRACT
MASLD frequently coexists with T2DM and sarcopenia through shared pathophysiological pathways, yet their synergistic impact on mortality remains poorly characterized. This study evaluated the interaction effects between sarcopenia and T2DM on mortality risk in MASLD patients. The Cox proportional hazard model was used to assess the hazard ratio (HR) for mortality. Three measures of interaction were computed, namely, the relative excess risk from interaction (RERI), the attributable proportion (AP), and the synergy index (SI), along with their CIs, utilizing delta techniques as outlined by Hosmer and Lemeshow. Among 1987 MASLD patients, 55.7% had neither sarcopenia nor T2DM, 19% had T2DM without sarcopenia, 16.1% had sarcopenia without T2DM, and 9.2% had sarcopenia with T2DM. According to 15-year median monitoring, adults with sarcopenia or T2DM were more likely to die from all causes and cardiovascular diseases (CVDs) than individuals without T2DM or sarcopenia. In contrast to patients without sarcopenia and T2DM, patients with concomitant sarcopenia and T2DM had a 2.5-fold greater risk of all-cause death and a doubled risk of death related to CVDs. Stratified analysis revealed a pronounced synergistic effect between sarcopenia and T2DM on mortality risk specifically in MASLD patients with advanced fibrosis. Sensitivity analyses confirmed this synergy was absent in non-MASLD. The rates of death from all causes and CVDs attributable to the combined effect of T2DM and sarcopenia were 27% and 29%, respectively. Sarcopenia-T2DM comorbidity synergistically elevates all-cause and CVD-related mortality in MASLD, particularly with advanced fibrosis, but not in non-MASLD.
PMID:41364036 | DOI:10.1096/fj.202503502R